Cytomegalovirus (CMV) is recognized as the most common cause of human congenital infection, occurring in up to 2.5% of all live births. Recent epidemiological studies have concluded that the impact of congenital CMV infection today is comparable to that of congenital rubella in the era before world-wide implementation or rubella immunization. In the United States congenital CMV has been identified as a leading cause of mental retardation, and it is estimated that sequellae of congenital CMV may account for as many as 40,000 new cases of sensorineural hearing loss per year. The pathogenesis of damage due to congenital infection with CMV in humans is, at present, poorly understood. This is primarily the result of the fact that viruses in the CMV group are species-specific and only recently has an appropriate animal model been identified. The guinea pig CMV (GPCMV) model is now recognized as closely resembling human CMV from both a virologic and histopathologic standpoint, and a reproducible model of viral labyrinthitis and hearing loss has been established in adult guinea pigs. We have confirmed that GPCMV also provides an excellent model for the investigation of congenital CMV infections. Maternal GPCMV infection during pregnancy causes congenital GPCMV inner ear infections and cochlear defects. Having demonstrated congenital GPCMV infection of the inner ear, we now propose to ascertain the optimal experimental conditions for a guinea pig model of congenital hearing loss for future systematic studies. The following basic questions concerning the pathogenesis of congenital GPCMV infections will be investigated: 1) What are the characteristics of GPCMV congenital infection within the fetal auditory system? 2) Does congenital infection of the fetal auditory system affect inner ear and central auditory pathway function? 3) Does postnatal reactivation of latent GPCMV in congenitally infected animals by immunosuppression produce infection and damage in the auditory system? 4) Can the auditory system's response to congenital GPCMV be used as a bioassay to test the efficacy of maternal vaccination? An interdisciplinary approach will be used to investigate the immunologic, virologic, electrophysiologic, morphologic, and metabolic aspects of this GPCMV model of human congenital CMV disease.